Advanced search
1 file | 5.35 MB

eIF1 modulates the recognition of suboptimal translation initiation sites and steers gene expression via uORFs

(2017) NUCLEIC ACIDS RESEARCH. 45(13). p.7997-8013
Author
Organization
Abstract
Alternative translation initiation mechanisms such as leaky scanning and reinitiation potentiate the polycistronic nature of human transcripts. By allowing for reprogrammed translation, these mechanisms can mediate biological responses to stimuli. We combined proteomics with ribosome profiling and mRNA sequencing to identify the biological targets of translation control triggered by the eukaryotic translation initiation factor 1 (eIF1), a protein implicated in the stringency of start codon selection. We quantified expression changes of over 4000 proteins and 10 000 actively translated transcripts, leading to the identification of 245 transcripts undergoing translational control mediated by upstream open reading frames (uORFs) upon eIF1 deprivation. Here, the stringency of start codon selection and preference for an optimal nucleotide context were largely diminished leading to translational upregulation of uORFs with suboptimal start. Interestingly, genes affected by eIF1 deprivation were implicated in energy production and sensing of metabolic stress.
Keywords
START CODON SELECTION, OPEN READING FRAMES, MESSENGER-RNA TRANSLATION, DEEP PROTEOME COVERAGE, EUKARYOTIC RIBOSOMES, ISOFORM EXPRESSION, MAMMALIAN-CELLS, UPSTREAM ORFS, DISCOVERY, QUANTIFICATION

Downloads

  • gkx469.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 5.35 MB

Citation

Please use this url to cite or link to this publication:

Chicago
Fijałkowska, Daria, Steven Verbruggen, Elvis Ndah, Veronique Jonckheere, Gerben Menschaert, and Petra Van Damme. 2017. “eIF1 Modulates the Recognition of Suboptimal Translation Initiation Sites and Steers Gene Expression via uORFs.” Nucleic Acids Research 45 (13): 7997–8013.
APA
Fijałkowska, D., Verbruggen, S., Ndah, E., Jonckheere, V., Menschaert, G., & Van Damme, P. (2017). eIF1 modulates the recognition of suboptimal translation initiation sites and steers gene expression via uORFs. NUCLEIC ACIDS RESEARCH, 45(13), 7997–8013.
Vancouver
1.
Fijałkowska D, Verbruggen S, Ndah E, Jonckheere V, Menschaert G, Van Damme P. eIF1 modulates the recognition of suboptimal translation initiation sites and steers gene expression via uORFs. NUCLEIC ACIDS RESEARCH. 2017;45(13):7997–8013.
MLA
Fijałkowska, Daria, Steven Verbruggen, Elvis Ndah, et al. “eIF1 Modulates the Recognition of Suboptimal Translation Initiation Sites and Steers Gene Expression via uORFs.” NUCLEIC ACIDS RESEARCH 45.13 (2017): 7997–8013. Print.
@article{8532029,
  abstract     = {Alternative translation initiation mechanisms such as leaky scanning and reinitiation potentiate the polycistronic nature of human transcripts. By allowing for reprogrammed translation, these mechanisms can mediate biological responses to stimuli. We combined proteomics with ribosome profiling and mRNA sequencing to identify the biological targets of translation control triggered by the eukaryotic translation initiation factor 1 (eIF1), a protein implicated in the stringency of start codon selection. We quantified expression changes of over 4000 proteins and 10 000 actively translated transcripts, leading to the identification of 245 transcripts undergoing translational control mediated by upstream open reading frames (uORFs) upon eIF1 deprivation. Here, the stringency of start codon selection and preference for an optimal nucleotide context were largely diminished leading to translational upregulation of uORFs with suboptimal start. Interestingly, genes affected by eIF1 deprivation were implicated in energy production and sensing of metabolic stress.},
  author       = {Fija\unmatched{0142}kowska, Daria and Verbruggen, Steven and Ndah, Elvis and Jonckheere, Veronique and Menschaert, Gerben and Van Damme, Petra},
  issn         = {0305-1048},
  journal      = {NUCLEIC ACIDS RESEARCH},
  keyword      = {START CODON SELECTION,OPEN READING FRAMES,MESSENGER-RNA TRANSLATION,DEEP PROTEOME COVERAGE,EUKARYOTIC RIBOSOMES,ISOFORM EXPRESSION,MAMMALIAN-CELLS,UPSTREAM ORFS,DISCOVERY,QUANTIFICATION},
  language     = {eng},
  number       = {13},
  pages        = {7997--8013},
  title        = {eIF1 modulates the recognition of suboptimal translation initiation sites and steers gene expression via uORFs},
  url          = {http://dx.doi.org/10.1093/nar/gkx469},
  volume       = {45},
  year         = {2017},
}

Altmetric
View in Altmetric
Web of Science
Times cited: